In the case of fracture or other injury to bone, proper bone healing and subsequent favorable bone remodeling is highly dependent on maintaining stability between bone fragments and, in the case of decalcified bone, on maintaining physiologic strain levels. External structural support can be gained using external braces, casts and the like. Internal structural support commonly is supplied by internal fixation devices such as bone plates, screws, intramedullar rods, etc., some of which may need to be surgically removed at a later time and all of which may prove to be burdensome and traumatic to a patient.
There is thus a need for a product that is a bone substitute product that is a bone graft material and that also provides structural support. This is especially so in the replacement or repair of long bones of the lower extremities and for use in spinal fusion techniques. Trauma, osteoporosis, severe osteo arthritis or rheumatoid arthritis, joint replacement, and bone cancers may call for treatment involving the use of structural bone substitute materials.
A successful bone graft requires an osteoconductive matrix providing a scaffold for bone ingrowth, osteoinductive factors providing chemical agents that induce bone regeneration and repair, osteogenic cells providing the basic building blocks for bone regeneration by their ability to differentiate into osteoblasts and osteoclasts, and structural integrity provided to the graft site suitable for the loads to be carried by the graft.
Current bone graft materials include autografts (the use of bone from the patient), allografts (the use of cadaver bone), and a variety of artificial or synthetic bone substitute materials. Autografts grafts are comprised of cancellous bone and/or cortical bone. Cancellous bone grafts provide virtually no structural integrity. Bone strength increases as the graft incorporates and new bone is laid down. For cortical bone, the graft initially provides some structural strength. However, as the graft is incorporated by the host bone, nonviable bone is removed by resorption significantly reducing the strength of the graft. The use of autograft bone may result in severe patient pain at the harvest site, and there is of course a limit to the amount of such bone that can be harvested from the patient. Allografts are similar to autografts in that they are comprised of cancellous and/or cortical bone with greater quantities and sizes being available. Sterilization techniques for allografts may compromise the structural and biochemical properties of the graft. The use of allograft bone bears at least some risk of transfer of disease and the risk that the graft may not be well incorporated.
For structural bone repair materials to be conveniently used, they must be capable of being formed into complex shapes that are designed to fit the contours of the repair site. An accurately contoured graft will enhance the integration of natural bone and provide better load carrying capability. Intimate, load carrying contact often is required between the natural bone and the bone substitute material to promote bone remodeling and regeneration leading to incorporation of the graft by host bone. Ideally, the strength and stiffness and resilience (that is, its response to load and rate of load) of the bone substitute material should be similar to those of natural bone.
A general overview of orthopedic implantable materials is given in Damien, Christopher J., and Parsons, Russell J., "Bone Graft and Bone Graft Substitutes: A Review of Current Technology and Applications," Journal of Applied Biomaterials. Vol. 2. pp. 187-208 (1991).
A variety of materials have been proposed for use as bone substitute materials, ranging from shaped porous metal objects suitable for defect filling around knee and hip joint replacements on the one hand to shaped ceramic materials on the other. Ceramic materials by and large have been formed through a sintering process in which a powder of a ceramic material such as zirconia is compressed to a desired shape in a mold and is then heated to sintering temperatures. The porosity of the resulting material is commonly quite low. Materials employing calcium phosphates (for example: fluorapatite, hydroxyapatite, and tricalcium phosphate) can also be sintered in this manner, the calcium phosphate having the capacity for acting as a substrate for bone growth (osteoconductivity).
It has been suggested to mix ceramic powders such as zirconia and hydroxyapatite, or fluorapatite and spinel, and then compress the mixture in a mold and either sinter or hot isostatically press to produce a somewhat porous ceramic of zirconia having pores at least partially filled with hydroxyapatite. Reference is made to Tamari et al., U.S. Pat. No. 4,957,509, and also Aksaci, D. et al., Porous Fluorapatite/spinel Osteoceramic for Bone Bridges, Ceramic Transactions, Vol. 48 p. 283 (1995). It has also been suggested to use ceramic articles having both high porosity and low porosity portions, and reference is made here to Hakamatsuka et al., U.S. Pat. No. 5,152,791, Johansson, U.S. Pat. No. 5,464,440 and Borom, U.S. Pat. No. 4,237,559.
See also Klawitter et al. U.S. Pat. No. 4,000,525. The latter reference refers to the use of an Al.sub.2 O.sub.3 slip that is foamed into a sponge, followed by filing.
By and large, metal or ceramic materials that have been proposed for bone substitutes have been of low porosity and have involved substantially dense metals and ceramics with semi-porous surfaces filled or coated with a calcium phosphate based material. The resulting structure has a dense metal or ceramic core and a surface which is a composite of the core material and a calcium phosphate, or a surface which is essentially a calcium phosphate. The bone substitute materials of this type commonly are heavy and dense, and often are significantly stiffer in structure than bone. Reference here is made to U.S. Pat. No. 5,306,673 (Hermansson et al.), U.S. Pat. No. 4,599,085 (Riess et al.), U.S. Pat. No. 4,626,392 (Kondo et al.), and U.S. Pat. No. 4,967,509 (Tamari et al.). Whereas natural bone, when stressed in compression, fails gradually (some components of the bone serving to distribute the load), bone substitute materials such as those described above commonly fail suddenly and catastrophically.
The present invention provides a strong composite article that is useful as a bone substitute material. The article comprises a supporting open skeleton or framework having interconnecting struts defining a plurality of interstices, the struts bearing a coating of a bioresorbable resilient material. Preferably, the article includes an osteoconductive material within the interstices and separated from the struts by the resilient material. The article may include materials that foster bone in-growth.
In one embodiment, the invention provides a strong article useful as a bone substitute material. The article comprises a continuous strong supportive framework having struts defining a plurality of interconnecting interstices throughout the bulk volume of the article, an osteoconductive material contained within the interstices, and a comparatively resilient interlayer which is bioresorbable and which is carried between and at least partially separates the supportive framework and the osteoconductive material. In response to physical stress imposed on the article, the interlayer serves to transmit and distribute loads within the article including hydraulic stiffening of the struts, in a manner similar to the response of natural bone to applied stress. Failure of the article is not sudden and catastrophic but rather is gradual. In this embodiment, the invention may be thought of as providing a strong composite article that is useful as a bone substitute material, the article being comprised of a supporting open skeleton or framework in the corpus of which are osteoconductive materials that are incorporated by or surrounded by bioresorbable resilient materials. The article may include materials that foster bone in-growth.
The supportive framework preferably is of a ceramic material having struts defining a plurality of interconnecting interstices throughout the bulk volume of the article, and an osteoconductive composition carried by said supporting framework and exposed to the interconnected openings. The osteoconductive composition occupies at least a portion of the same bulk volume as the framework component. Desirably, the supportive framework has void volumes that are in the range of 20% to 90% and preferably at least 50%. Further, the mean size of the openings of the supportive framework component desirably are at least 50 .mu.m and preferably are in the range of 200 .mu.m to 600 .mu.m.
The polymeric material is a bioresorbable polymer which may be one or a combination of: collagen, poly-lactic acid, poly-glycolic acid, copolymers of lactic acid and glycolic acid, chitosan, chitin, gelatin, or any other resorbable polymer. This polymer material may be used alone, may be reinforced with a particulate or fibrous biocompatible material, and the composite may include a biological agent known to induce bone formation. This polymeric material will resorb as host bone grows into the interstices to replace it.
The osteoconductive composition, though it may also be a continuous interconnected body, is smaller in volume than the spaces in the framework interstices; thus there is a gap between it and the framework struts. This gap is filled with a bioresorbable resilient material so as to provide an energy absorbing interface that serves to provide load distribution and a hydraulic shock absorbing function. The osteoconductive composition may, instead, be added during a surgical procedure to the interstices of a supportive framework, the struts of which have been coated with a resilient material.
In a preferred embodiment, the supportive framework, the osteoconductive composition and the resilient, bioresorbable material each are continuous three dimensional structures that exhibit 3,3 connectivity and occupy at least a portion and preferably the entirety of the same bulk volume, each continuous structure having interconnected openings that interconnect with the openings of the other. Here, the resilient layer serves to transfer and distribute load from the supportive framework to the osteoconductive material, increasing the strength of the structure and tending to avoid brittle behavior under maximum material conditions. It is believed that the resulting article will transfer stress to the surrounding bone in a more physiologic way than does a dense ceramic or metal body. This stress transfer is important in stimulating bone growth and remodeling surrounding the graft, and avoiding "stress shielding," which is known to elicit an adverse bone remodeling response.
In yet another embodiment, the struts are comprised of a mixture or composite which contains the supportive material as well as osteoconductive material, the support material providing strength to the article and the osteoconductive material being carried at least partially on the surface of the interstices so as to be exposed to the interconnected openings to provide an osteoconductive environment favoring bone growth. The struts are coated with, or the interstices contain a bioresorbable, resilient material.
In a further embodiment, the supportive framework comprises struts that are coated with a bioresorbable resilient material to define interstices that open onto surfaces of the article and that can be filled with a calcium phosphate cement during a surgical procedure. In this embodiment, the calcium phosphate cement hardens within the interstices and the resilient material separating the supportive framework from the hardened calcium phosphate cement acts to cushion forces that are generated by exterior loads on the framework.
In yet another embodiment, the interstices of the strong framework are filled with a composite of a biocompatible, bioresorbable resilient material as a matrix containing particles of calcium phosphate or other osteoconductive material.
In yet a further embodiment, the invention comprises an open celled article of any of the several types described above and including a second substantially dense continuous material component attached to a surface of the bulk volume of the first material, the second component having a porosity not greater than 10% of its bulk volume. This substantially dense phase may be either a ceramic, a polymer, a metal, or a composite material.